The present invention relates to a myelomonocytic differentiation antigen and, more particularly to CD14.
Differentiation of myelomonocytic cells from pluripotent stem cells to mature, functioning monocytes/macrophages and granulocytes is accompanied by a variety of changes including the expression of new cell surface antigens. [K. A. Foon and R. F. Todd III, Blood 68, 1 (1986).] One such antigen, CD14, recognized by a number of monoclonal antibodies (mAbs) including MO2, MY4, and LeuM3 [S. M. Goyert et al., J. Immunol. 137, 3909 (1986); S. M. Goyert and E. Ferrero, in Leukocyte Typing III, A. McMichael et al., Eds. (Oxford Univ. Press, Oxford, 1987), pp. 613-619], is a 53-kDa glycoprotein expressed by monocytes, macrophages [R. F. Todd III et al., in Leukocyte Typing, A. Bernard, L. Boumsell, J. Dausset, C. Milstein, S. F. Schlossman, Eds. (Springer-Verlag, New York, 1984), pp. 424-433; J. D. Griffin and S. F. Schlossman, ibid., pp. 404-410; N. Hogg and M. A. Horton, in Leukocyte Typing III, A. McMichael et al., Eds. (Oxford Univ. Press, Oxford, 1987), pp. 576-602], and activated granulocytes [N. Hogg and M. A. Horton, in Leukocyte Typing III, A. McMichael et al., Eds. (Oxford Univ. Press, Oxford, 1987), pp. 576-602; C. Buckle and N. Hogg, personal communication].
The restricted expression of this molecule on mature cells suggests an important effector function.
The CD14 gene is located in a region of chromosome 5 containing a cluster of genes that encode several myeloid-specific growth factors [interleukin-3, granulocyte-macrophage colony-stimulating factor, and macrophage colony-stimulating factor (CSF-1) or growth factor receptors (FMS, receptor for CSF-1) [M. M. LeBeau et al., ibid. 231, 984 (1986); M. M. LeBeau et al., Proc. Natl. Acad. Sci. U.S.A. 84,5913 (1987); M. J. Pettenati et al., ibid., p. 2970], as well as other growth factor and receptor genes [platelet-derived growth factor receptor, B2-adrenergic receptor, and endothelial cell growth factor [HGM9: Ninth International Workshop on Human Gene Mapping (1987), Cytogenet. Cell Genet., in press]. The mapping of the CD14 gene to this region of chromosome 5, its expression preferentially by mature myeloid cells, and its deletion in the malignant cells of patients having myeloid leukemias and a del(5q) suggest that the CD14 antigen may also serve as some type of receptor or factor and that a role for this gene in the pathogenesis of myeloid disorders should be considered. The CD14 antigen is thus useful in the diagnosis of mature myeloid leukemia.
The potential uses of CD14 in the medical and scientific fields are, of course, limited by its natural availability.
Accordingly, it is an object of the present invention to provide recombinant myelomonocytic differentiation antigen CD14.
Another object is to provide such protein which has a primary amino acid sequence substantially equivalent to that of native human CD14.
A further object is to provide a recombinant DNA sequence which comprises the coding sequence for CD14.
Still another object is to provide a replicative cloning vector which comprises the sequence encoding CD14 or a portion thereof and a replicon operative in prokaryotic or eukaryotic cells.
It is also an object to provide an expression system which comprises a DNA sequence encoding CD14 operably linked to suitable control sequences.
It is another object to provide recombinant host cells transformed with such an expression system.
It is a further object to provide a method of producing recombinant CD14.
Another object is to provide a clone of CD14.
A still further object is to provide a process for isolating a DNA clone encoding CD14.